PhD, Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226.
Endocrinology. 2013 Dec;154(12):4768-76. doi: 10.1210/en.2013-1160. Epub 2013 Oct 3.
Hyperaldosteronism is linked to the development and progression of several different cardiovascular diseases. Angiotensin (Ang) II increases aldosterone secretion and adrenal blood flow. Ang II peptide fragments are produced by various peptidases, and these Angs have diverse and vital physiologic roles. Due to the uncharacteristic vasorelaxation of adrenal arteries by Ang II, we tested the hypothesis that Ang II metabolism contributes to its relaxant activity in adrenal arteries. Metabolism of Angs by bovine adrenal cortical arteries and isolated bovine adrenal vascular cells was measured by liquid chromatography-mass spectrometry. The primary Ang metabolites of adrenal arteries are Ang III and Ang (1-7), with Ang IV produced to a lesser extent. Bovine microvascular endothelial cells produced a similar metabolic profile to adrenal arteries, whereas bovine adrenal artery smooth muscle cells exhibited less metabolism. In preconstricted adrenal arteries, Ang II caused relaxation in picomolar concentrations and constrictions at 10nM. Ang-converting enzyme 2 inhibition augmented this relaxation response, whereas aminopeptidase inhibition did not. Ang III was equipotent to Ang II in relaxing adrenal arteries. Ang IV did not cause relaxation. Nitric oxide synthase inhibition enhanced Ang II-induced constriction of adrenal arteries. Aminopeptidase inhibition increased the concentration range for Ang II-induced constriction of adrenal arteries. Ang III and Ang IV did not change the basal tone but caused constriction of adrenal arteries with nitric oxide synthase inhibition. These data indicate that Ang II metabolism modulates the vascular effects of Ang II in the adrenal vasculature.
醛固酮增多症与多种心血管疾病的发生和发展有关。血管紧张素（Ang）II 可增加醛固酮的分泌和肾上腺血流。血管紧张素肽片段由各种肽酶产生，这些 Ang 具有多样且重要的生理作用。由于 Ang II 对肾上腺动脉的血管舒张作用不典型，我们检测了 Ang II 代谢对其在肾上腺动脉中舒张活性的影响的假说。通过液相色谱-质谱法测量牛肾上腺皮质动脉和分离的牛肾上腺血管细胞中 Angs 的代谢。肾上腺动脉的主要 Ang 代谢物是 Ang III 和 Ang（1-7），而 Ang IV 的产生程度较低。牛微血管内皮细胞产生与肾上腺动脉相似的代谢谱，而牛肾上腺动脉平滑肌细胞的代谢较少。在预先收缩的肾上腺动脉中，Ang II 在皮摩尔浓度下引起舒张，在 10nM 时引起收缩。血管紧张素转换酶 2 抑制增强了这种舒张反应，而氨基肽酶抑制则没有。Ang III 在舒张肾上腺动脉方面与 Ang II 具有同等效力。Ang IV 不会引起舒张。一氧化氮合酶抑制增强了 Ang II 引起的肾上腺动脉收缩。氨基肽酶抑制增加了 Ang II 引起的肾上腺动脉收缩的浓度范围。Ang III 和 Ang IV 不会改变基础张力，但会在一氧化氮合酶抑制下引起肾上腺动脉收缩。这些数据表明，Ang II 代谢调节了 Ang II 在肾上腺血管中的血管作用。
